The high incidence of neurodegenerative and/or neurological diseases is a problem of the first order worldwide. Therefore, it is necessary to search for neuroprotective compounds preventing or alleviating said diseases. Alzheimer's disease (AD) is the most prevalent among said diseases. Current drugs offer few benefits to patients, so it is necessary to search for neuroprotective compounds to alleviate this disease.
Since these drugs have had little success, new lines of research have opened up and, among them, research on inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) enzyme (better known as statins) as therapeutic agents stands out in recent years. In fact, a significant reduction of the risk of Alzheimer's has been described in patients treated with statins (Jick H, Zornberg G L, Jick S S, Seshadri 5, Drachman D A. Statins and the risk of dementia. Lancet. 2000. 356: 1627-1631). In the case of AD, several phase II clinical trials using mainly atorvastatin and simvastatin have been conducted in recent decades. However, up until now said studies were not capable of demonstrating the therapeutic efficacy of statins in Alzheimer's disease (Burgos J S, Benavides J, Douillet P, Velasco J, Valdivieso F. How statins could be evaluated successfully in clinical trials for Alzheimer's disease? Am J Alzheimers Dis Other Demen. 2012. 27(3): 151-153).
It is known in the state of the art (EP2241561) that modifications in the hexahydronaphthalene ring structure of certain statins results in statins (NST0037) with a high hypocholesterolemic and neuroprotective capacity. It had been previously identified that methylation in the β-hydroxypyranone ring in simvastatin produced a derivative with in vitro HMGCR inhibitory capacity which translated into an in vivo hypocholesterolemic effect (U.S. Pat. No. 6,541,511 B1), although this document does not refer to the neuroprotective capacity of said modified statin.
There is a need today to develop new compounds, particularly statins, with therapeutic efficacy in neurodegenerative diseases, i.e., compounds with high neuroprotective activity which additionally have a good blood-brain barrier passage.